It has been shown that endogenous opioids are released in the CNS during acupuncture or electroacupuncture (EA) stimulation, and that they are operative in mediating its analgesic effect (Ann Rev Pharmacol Toxicol 22:193, 1982). However it is still not clear (1) which kind of endogenous opioids is actually released in response to EA of given parameters; (2) why EA is effective in certain patients of experimental animals (responders) but not in others (nonresponders); and (3) why the effect of EA analgesia fades away after prolonged stimulation (tolerance to EA). To solve these problems we intend to use the following approaches: (1) Antibody microinjection technique (Neuropharmacology 23:1, 1984) will be used in which specific antibodies against opioid peptides are injected intracerebrally or intrathecally to bind the peptide and prevent it from receptor activation. Preliminary results have shown that low (2 Hz) and high (100 Hz) frequency EA analgesia can be blocked by intrathecal injection of (Met) enkephalin (ME) antibodies and dynorphin A (DYN) antibodies, respectively, indicating that EA of different frequencies releases different opioids in the spinal cord. (2) CCK-8 has been suggested as endogenous antagonist of opioid peptides. It is hypothesized that in sufficient release of opioids and surplus release of CCK-8 may be implicated, at least in part, in the "nonresponder" to EA analgesia. Preliminary results have shown that intrathecal injection of CCK-8 antiserum was capable of changing nonresponders into responders and postponing the development of EA tolerance. (3) Spinal subarachnoid space perfusion will be used for measuring the release of certain neuropeptides elicited by EA of different parameters and various durations. Through these studies we hope to remove this thousand years old technique from the realm of trail-and-error and pure tradition, and to find out optimal conditions to increase the efficacy of EA analgesia, and in the meantime to add knowledge to the understanding of opioid peptides and analgesia.